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A Homely Rodent May Hold Cancer-Fighting Clues

Is the naked mole rat a cancerproof rodent? New research shows that the animals produce a unique compound that appears to protect them against the disease.Credit
Brandon Vick/University of Rochester

The laboratory of Vera Gorbunova and Andrei Seluanov, a husband-and-wife team of biologists at the University of Rochester, has the feel of a petting zoo. They maintain colonies of several species of rodents — some familiar, like mice and guinea pigs, and some much more exotic, like blind mole rats from Israel and naked mole rats from East Africa.

Amusing children with furry creatures is not their goal, however. The biology of animals is mysteriously diverse, and lurking within it may be clues to new kinds of medicine.

Even the strangest creatures may hold a valuable surprise. And in the latest issue of the journal Nature, Dr. Gorbunova, Dr. Seluanov and their colleagues report a particularly fascinating surprise: Naked mole rats produce a unique compound that appears to block them from getting cancer.

Rochelle Buffenstein, who studies the biology of naked mole rats at the University of Texas Health Science Center, called the discovery by Dr. Gorbunova and Dr. Seluanov “intriguing and most unexpected.” She is hopeful that the naked mole rat’s secrets may inspire new treatments for cancer.

Dr. Gorbunova and Dr. Seluanov are hopeful as well; they’re now investigating whether the compound can protect mice from cancer. “We think this mechanism could be moved into humans,” Dr. Gorbunova said.

Studying cancer in animals is nothing new, of course. Scientists regularly test out potential cancer drugs on mice. More recently, however, researchers have started to appreciate the differences among various species. Lab mice are especially prone to cancer, for example; 47 percent of them develop tumors of one sort or another. Naked mole rats, on the other hand, have a profoundly different sort of life. They can live more than 30 years, and scientists have yet to find a single mole rat with cancer.

To understand this phenomenon, scientists have examined the naked mole rats’ cells. They’ve infected them with viruses that reliably trigger cancer in mouse cells, finding that their efforts fail utterly in naked mole rat cells.

This resistance has inspired Dr. Gorbunova and Dr. Seluanov to figure out the naked mole rat’s secret. “There’s a lot to be learned from cancerproof rodents,” Dr. Gorbunova said.

In 2009, Dr. Gorbunova and Dr. Seluanov found an intriguing clue to how naked mole rats escape cancer. In humans, mice and most other mammals, cells will grow and divide until they bump into other cells. The contact causes them to stop dividing or even die off. This response — called contact inhibition — stops cells from multiplying out of control.

Photo

Carl ZimmerCredit
Earl Wilson/The New York Times

But Dr. Gorbunova, Dr. Seluanov and their colleagues discovered that naked mole rat cells are much more sensitive to other cells. They stop growing at a third the density that the mouse cells do.

They also discovered that raising naked mole rat cells can be frustrating. To raise cells, scientists put them in a liquid full of nutrients. After a few days, the scientists noticed, naked mole rat cells turn that liquid to syrup. “We said, ‘We need to find out what this goo is,'” said Dr. Gorbunova.

Their postdoctoral researcher, Christopher Hine (now at Harvard), discovered that the goo was made up of chain-shaped molecules called hyaluronan. Hyaluronan is a common molecule in human bodies; it’s an ingredient in the stretchy gel in which our cells are embedded. It also sends signals into our cells by latching onto a receptor on cells called CD44. The signals can deliver commands to cells to change course — to start multiplying in some cases, for example.

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The Rochester team found that the bodies of naked mole rats are loaded with high levels of hyaluronan. But they discovered something else: Naked mole rats make a form of hyaluronan that’s five times as long as the kind made by mice or humans.

The scientists wondered if this long hyaluronan helped naked mole rats fight cancer. They added hyaluronan-destroying enzymes to populations of naked mole rat cells to see what would happen. Instead of arresting their growth at a low density, the cells now grew into thick clusters, just as cancer-prone mouse cells do.

The scientists next shut down the gene in naked mole rat cells that encodes hyaluronan. They then inserted a cancer-causing virus. Instead of resisting the virus, the hyaluronan-free cells multiplied wildly. And when the researchers moved the naked mole rat cancer cells into mice, the cells grew into full-blown tumors. Suddenly, naked mole rat cells became as vulnerable to cancer as mouse cells — or human cells.

Dr. Gorbunova and Dr. Seluanov suspect that the long form of hyaluronan made by naked mole rats didn’t originally evolve to fight cancer. Hyaluronan helps make skin stretchy, and naked mole rats are especially stretchy. “If you grab an animal, it feels like you’re removing their skin,” Dr. Seluanov said.

The long form of hyaluronan may have first evolved as an important adaptation for animals that have to wiggle through tight, rocky tunnels underground. It may have been a fortunate accident that the molecule also sent a signal to cells through the CD44 receptor that stopped them from becoming cancerous.

Hyaluronan probably isn’t the only way to fight off cancer. Blind mole rats (which, despite their name, are not close relatives of naked mole rats) rarely get cancer either. But the research Dr. Gorbunova and Dr. Seluanov have conducted on those rodents suggests that they fight cancer by sending a different signal to fast-growing cells, causing them to commit suicide.